GREM2 and Nephropathy: Although previous studies by our group demonstrated that Grem2 increasing induced by high glucose could mediate podocyte apoptosis (Wen et al. 2019), and indeed we also found that the Grem1 and Grem2 were both upregulated in the DM vs. Con group; however, the present findings showed that Grem1 was the most responsive to nicotine-exacerbated kidney damage in DN compared to Germ2.